This project is concerned with two neuropeptides, cholecystokinin (CCK) and met5-enkephalin-arg6-gly7-leu8 (YGGFMRGL) and an attempt to evaluate whether in the spinal cord, these two peptides are involved in sensory processing, in particular pain; in fact, YGGFMRGL injection in the subarachnoid space suppresses pain sensation whereas CCK blocks this action. In spinal cord, the highest levels of YGGFMRGL and CCK are found in laminae I and II, respectively. Two molecular weight forms of YGGFMRGL were found in the spinal cord, the first is identical to authentic YGGFMRGL; the second is a 5.3 Kd N-terminal extended form. Release was studied with an in vivo perfusion system of the subarachnoid space of the cord coupled with bilateral electrical stimulation of the sciatic nerves. High and low molecular weight forms which are present in spinal cord are released upon stimulation suggesting both forms participate in neuromodulation. A model of chronic inflammation using hindpaw injections of Freund's adjuvant is being studied as an attempt to relate pain with changes in the dynamic state of endogenous CCK, YGGFMRGL and dynorphin. Profound steady state changes of dynorphin occur in the dorsal horn to which the sensory fibers of the affected limb project. CCK and other peptides that block the analgesic action of opiates are also being examined in this condition. These studies on spinal cord are relevant to sensory processing, in particular pain, and may be important in understanding CNS neurochemical changes due to inflammation and other chronic pain states.